Summary: The class 2/3 (PorB) OMP, a porin of Neisseria meningitidis, has eight predicted surface exposed loops. The gene encoding this protein is different between different serotypes in regions corresponding to several of these loops. Antibodies to PorB are bactericidal and antigenic diversity between these proteins forms the basis of the current serotyping classification. Previously in our laboratory a PorB variable region (VR) typing method and PCR method amplifying porB directly from cerebrospinal fluid were developed. These methods were used to examine a large number of CSF samples from individuals with sepsis or meningitis from Brazil, and to examine the genetic basis for the unusual serotype of Chilean strain 501. Subsequent rabbit immunization studies using this strain revealed immunodominance of individual epitopes corresponding to particular variable regions of the porin protein. We have explored methods using cyclic peptides to mimic individual PorB loops in immunization studies to further our understanding of the effect of PorB loop variation on immune responses. We are currently examining the diversity of human antibody responses to the PorB protein following group B meningococcal infection. Using Western Blot analysis of post infection sera with a panel of strains, we are identifying variable region specific human responses. In this study we are investigating the human relevance of the immunodominance observed in our earlier studies with the Ch501 strain in rabbits and cyclic peptides in mice. We have also expanded our earlier genetic typing method and adapted it to the checkerboard hybridization method used in our laboratory for gonococcal porB VR typing.